The success of organ or living tissue transplantation depends greatly on the preservation of the tissue activity (e.g., tissue or organ viability) at the time of harvest of the organ from a donor, during storage of the harvested organ, and at transplantation. To date, preservation of organs such as lungs, pancreas, heart and liver remains a significant stumbling block to the successful transplantation of these organs. Tissues and organs for transplantation are subject to the tissue destructive effects associated with the body's inflammatory response, which typically is stimulated in response to an initial tissue injury. Accordingly, organs and tissues to be transplanted are at risk of tissue damage following their removal from a donor, during storage and upon transplantation. It is also currently believed that the tissue damage to transplanted tissue may in large part be due to ischemia-reperfusion injury to the organ after it has been transplanted in the organ recipient.
U.S. Pat. No. 4,952,409 describes a superoxide dismutase-containing liposome to inhibit reperfusion injury. U.S. Pat. No. 5,002,965 describes the use of ginkolides, known platelet activating factor antagonists, to inhibit reperfusion injury. Both of these factors are described as working primarily by inhibiting the release of and/or inhibiting the damaging effects of free oxygen radicals. A number of patents also have issued on the use of immunosuppressants for inhibiting graft rejection. A representative listing includes U.S. Pat. Nos. 5,104,858, 5,008,246 and 5,068,323. A significant problem with many immunosuppressants is their low therapeutic index, requiring the administration of high doses that can have significant toxic side effects.
Therefore, an object of the present invention is to provide compositions and methods for enhancing the viability of mammalian living tissues and organs to be transplanted, including protecting the tissues and organs to be transplanted from immune cell-mediated tissue destruction, including the tissue damage associated with ischemia-reperfusion injury. Another object is to provide a preservation solution for maintaining harvested organs and living tissues that is capable of enhancing the viability of the harvested organs and tissues, including protecting them from tissue damage, particularly immune cell-mediated tissue damage. Still another object is to provide compositions and methods for protecting transplanted tissues and organs from tissue damage, particularly immune cell-mediated tissue damage, including the tissue damage associated with ischemia-reperfusion injury.
These and other objects and features of the invention will be apparent from the description, drawings and claims which follow.